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Method for preparing (R)-2-hydroxyl-2-trifluoromethyl-4-methyl-4-ethyl pentenoate under asymmetric catalysis at low temperature

A technology for ethyl pentenoate and catalytic preparation, applied in asymmetric synthesis, organic chemistry methods, chemical instruments and methods, etc., can solve problems such as high price of asymmetric catalysts, and achieve high yield and good stereoselectivity Effect

Inactive Publication Date: 2014-03-26
SUZHOU HUIHE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Optically pure ( R )-2-Hydroxy-2-trifluoromethyl-4-methyl-4-pentenoic acid ethyl ester general problem is: the price of asymmetric catalyst is relatively expensive, and the dosage of catalyst is about 5%-10% equivalent , there is no particularly efficient way to reduce the amount of catalyst without affecting the activity of the reaction, which is a key issue in the preparation of this compound

Method used

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  • Method for preparing (R)-2-hydroxyl-2-trifluoromethyl-4-methyl-4-ethyl pentenoate under asymmetric catalysis at low temperature
  • Method for preparing (R)-2-hydroxyl-2-trifluoromethyl-4-methyl-4-ethyl pentenoate under asymmetric catalysis at low temperature

Examples

Experimental program
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Effect test

Embodiment 1

[0034] Example 1: Preparation of pure (R)-2-hydroxy-2-trifluoromethyl-4-methyl-4-pentenoic acid ethyl ester with a yield of 90% and an ee value of 98%.

[0035] Preferably (Pd / Sunphos, Ligand L1, Ar=phenyl) take ethyl trifluoropyruvate (8.505 g, 50 mmol, 1 eq) and place it in a baked reaction tube, and prepare the prepared catalyst as catalyst Solution, measured with a syringe (0.80 mL, concentration 8 g / L, 5 μmol, 0.01% eq) and added to the reaction system, stirred at room temperature for 30 minutes, then cooled the reaction system to -15 ~-20 o C. Add the prepared isobutene solution (364 g / L, solvent is toluene) into the reaction system to start the reaction. After the reaction was finished, post-treatment and distillation were carried out to obtain a colorless oily pure product. The resulting pure product has an enantiomeric excess of 98%: Rf = 0.59 (ethyl acetate : petroleum ether = 1 / 50), boiling point 97-103°C (60 mmHg); [α] D 23.7 = -6.8 o (c = 2.47, CHCl 3 ); H-N...

Embodiment 2

[0036] Example 2: Preparation of pure (R)-2-hydroxy-2-trifluoromethyl-4-methyl-4-pentenoic acid ethyl ester with 88% yield and 95% ee value.

[0037] Preferably (Pd / Sunphos, Ligand L2, Ar=4-methylphenyl) take ethyl trifluoropyruvate (8.505 g, 50 mmol, 1eq) and place it in a baked reaction tube, and prepare the The catalyst was prepared as a catalyst solution, which was measured with a syringe (0.82 mL, concentration 8.2 g / L, 5 μmol, 0.01% eq) and added to the reaction system, stirred at room temperature for 30 minutes, and then the reaction system was placed in an ice-salt bath Cool down to -15~-20 o C. Add the prepared isobutene solution (364 g / L, solvent is toluene) into the reaction system to start the reaction. After the reaction is finished, post-treatment and distillation are carried out to obtain the pure product.

Embodiment 3

[0038] Example 3: Preparation of pure (R)-2-hydroxy-2-trifluoromethyl-4-methyl-4-pentenoic acid ethyl ester with a yield of 65% and an ee value of 88%.

[0039] (Pd / Sunphos, Ligand L3 , Ar=3,5-dimethylphenyl) weigh ethyl trifluoropyruvate (8.505 g, 50 mmol, 1 eq) and place it in a baked reaction tube, prepare the prepared catalyst as a catalyst solution, Measure (1.01 mL, concentration 10.1 g / L, 5 μmol, 0.01%eq) with a syringe and add to the reaction system, stir at room temperature for 30 minutes, then cool the reaction system to -15~- 20 o C. Add the prepared isobutene solution (364 g / L, solvent is toluene) into the reaction system to start the reaction. After the reaction is finished, post-treatment and distillation are carried out to obtain the pure product.

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Abstract

The invention discloses a method for preparing (R)-2-hydroxyl-2-trifluoromethyl-4-methyl-4-ethyl pentenoate under asymmetric catalysis at a low temperature, wherein an asymmetric catalyst system is prepared as a catalyst through Carbonyl-ene reaction; and the high-optical purity (R)-2-hydroxyl-2-trifluoromethyl-4-methyl-4-ethyl pentenoate is prepared under the reaction condition of an ice-salt bath by controlling the temperature of the asymmetric catalysis in the range from -15 DEG C to -20 DEG C and the reaction time in the range from 1 to 3 hours. The method provided by the invention has the advantages of controllable reaction conditions, good stereoselectivity and high yield.

Description

technical field [0001] The invention relates to a method for preparing (R)-2-hydroxyl-2-trifluoromethyl-4-methyl-4-pentenoic acid ethyl ester of high optical purity, more particularly to a method using metal palladium Synthesis of bidentate chiral phosphine ligand SunPhos with C2 axis of symmetry as an efficient method for the asymmetric preparation of catalytic systems. Background technique [0002] Before the 1960s, heterogeneous catalysis was the main method. Heterogeneous asymmetric catalysis can only give 10-15% e.e. of the product. In 1965 Wilkson discovered the homogeneous catalyst, Rh(Ph 3 P) 3 Cl, good solubility and high activity. In 1968, Honer and Knowles respectively reported the asymmetric homogeneous catalytic hydrogenation of double bonds. In 1971, Kagan made a breakthrough, using DIOP to catalyze a product with 72% e.e. In 1972, Knowles obtained an enantioselectivity greater than 95% e.e. with DIPAMP chiral catalyst. Subsequently, there are more and m...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C69/732C07C67/343C07B53/00B01J31/24
CPCC07C67/343C07C69/732
Inventor 李新涓子汪迅李勇刚张兆国高艳吕兴红沈小良王卓夏小波
Owner SUZHOU HUIHE PHARMA
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